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Pro-nerve growth factor in the ovary and human granulosa cells

  • Sabine Meinel , Jan Blohberger , Dieter Berg , Ulrike Berg , Gregory A. Dissen , Sergio R. Ojeda and Artur Mayerhofer EMAIL logo
Published/Copyright: October 10, 2015
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Hormone Molecular Biology and Clinical Investigation
From the journal Hormone Molecular Biology and Clinical Investigation Volume 24 Issue 2

Abstract

Background: Pro-nerve growth factor must be cleaved to generate mature NGF, which was suggested to be a factor involved in ovarian physiology and pathology. Extracellular proNGF can induce cell death in many tissues. Whether extracellular proNGF exists in the ovary and may play a role in the death of follicular cells or atresia was unknown.

Materials and methods: Immunohistochemistry of human and rhesus monkey ovarian sections was performed. IVF-derived follicular fluid and human granulosa cells were studied by RT-PCR, qPCR, Western blotting, ATP- and caspase-assays.

Results and conclusion: Immunohistochemistry of ovarian sections identified proNGF in granulosa cells and Western blotting of human isolated granulosa cells confirmed the presence of proNGF. Ovarian granulosa cells thus produce proNGF. Recombinant human proNGF even at high concentrations did not affect the levels of ATP or the activity of caspase 3/7, indicating that in granulosa cells proNGF does not induce death. In contrast, mature NGF, which was detected previously in follicular fluid, may be a trophic molecule for granulosa cells with unexpected functions. We found that in contrast to proNGF, NGF increased the levels of the transcription factor early growth response 1 and of the enzyme choline acetyl-transferase. A mechanism for the generation of mature NGF from proNGF in the follicular fluid may be extracellular enzymatic cleavage. The enzyme MMP7 is known to cleave proNGF and was identified in follicular fluid and as a product of granulosa cells. Thus the generation of NGF in the ovarian follicle may depend on MMP7.

Keywords: granulosa cells; human ovary; matrix metalloprotease; neurotrophin
Corresponding author: Artur Mayerhofer, MD, BioMedizinisches Centrum (BMC), Ludwig-Maximilian-University (LMU), Cell Biology, Anatomy III, Großhaderner Str. 9, D-82152 Planegg, Germany, Phone: +049 89 2180 75859, Fax: +049 89 2180 75882, E-mail:

Acknowledgments

We gratefully acknowledge the skillful help of Daniel Einwang, Astrid Tiefenbacher, Carola Hermann and the editorial support by Karin Metzrath.

Grant information/competing interests: DFG MA 1080/17-3 and in part by MA1080/19-1 and NIH grant 8P51OD011092 (G.A.D., S.R.O.) for the operation of the ONPRC.

This work was done in partial fulfillment of the requirements for Dr.rer.nat. projects of SM and JB at the LMU. There are no competing interests.

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Received: 2015-7-8
Accepted: 2015-8-21
Published Online: 2015-10-10
Published in Print: 2015-11-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Topic B: Neuroendocrine Control, Gonadal Function, PCOS/Insulin Sensitivity and Reproduction
  3. Review Articles
  4. Prokineticins in central and peripheral control of human reproduction
  5. Role of the teneurins, teneurin C-terminal associated peptides (TCAP) in reproduction: clinical perspectives
  6. Original Articles
  7. Pro-nerve growth factor in the ovary and human granulosa cells
  8. Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients
https://doi.org/10.1515/hmbci-2015-0028
Keywords for this article
granulosa cells; human ovary; matrix metalloprotease; neurotrophin

Articles in the same Issue

  1. Frontmatter
  2. Topic B: Neuroendocrine Control, Gonadal Function, PCOS/Insulin Sensitivity and Reproduction
  3. Review Articles
  4. Prokineticins in central and peripheral control of human reproduction
  5. Role of the teneurins, teneurin C-terminal associated peptides (TCAP) in reproduction: clinical perspectives
  6. Original Articles
  7. Pro-nerve growth factor in the ovary and human granulosa cells
  8. Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients
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